BIODEGRADABLE CONTROLLED RELEASE TABLETS .1. PREPARATIVE VARIABLES AFFECTING THE PROPERTIES OF POLY(LACTIDE-CO-GLYCOLIDE) COPOLYMERS AS MATRIX FORMING MATERIAL

A detailed study of the synthesis of poly(lactide-co-glycolide) copolymers for use as biodegradable polymers in the preparation of controlled release implantable matrix tablets has been undertaken. The factors examined were the catalyst (type and concentration), co-catalyst concentration and time and temperature of polymerization. The samples were examined for their molecular weight by viscometry, composition by H-1-NMR spectroscopy, microstructure by C-13-NMR spectroscopy and morphology by differential scanning calorimetry. The percentage yield and the reproducibility of polymerization were also investigated. Comparison of two widely used catalysts - antimony trifluoride and stannous octoate - revealed that stannous octoate was far more effective and this catalyst was investigated further. At both low and high levels of temperature, with increasing the catalyst level there was an initial sharp increase in the molecular weight but this passed through a maximum before falling at higher catalyst levels. The effective catalyst concentrations depend on the temperature of polymerization and higher molecular weight polymers were obtained at the lower temperature. Temperatures in excess of 190-degrees-C caused polymer decomposition. The high molecular weight polymers were hard, but not brittle, "elastic" materials which might limit their application in tableting. The percentage yield is less affected by the temperature than by the catalyst level. The change in percentage yield with respect to the catalyst level followed the same pattern as the change in molecular weight. Increased levels of co-catalyst (lauryl alcohol) caused both a lowering of molecular weight and percentage yield. At both levels of temperature the molecular weight and percentage yield increased up to 4 h reaction time, but the molecular weight fell at longer reaction times whilst the percentage yield remained essentially constant. The composition of the samples was affected by the polymerization time. However, the composition did not change at reaction times longer than 4 h. From these results it appears that 4 h is the optimum polymerization time. All samples produced have been shown to be block copolymers which were amorphous and whose glass transition temperatures depended on composition and molecular weight. Glass transition temperatures as low as 37-degrees-C were measured which could have a significant effect on drug release, when formulated as implanted tablets.